The over-arching theme of this proposal is to train comprehensive imaging scientists in the skills necessary to identify clinically relevant problems; develop instrumentation, sensors, and contrast agents to form images appropriate for the problem; and analyze the resulting imaging data using signal processing, mathematical modeling, visualization, and informatics techniques to improve the prevention, detection, diagnosis, and treatment of human diseases. The program spans from molecular to cellular to tissue to organ. In order for imaging scientists to be knowledgeable of the full trajectory from image formation to analysis and decision-making, they must be trained in four core areas: Instrumentation, Devices, and Contrast Agents; Image processing; Modeling and Visualization; and Informatics. All students in the program are trained in the core concepts of these areas. The current training program is a two year pre-doctoral portfolio program. A total of 20 students have been admitted to the program. The proposed renewal will train another 16 students. The program includes off-campus externship research experiences and a wide-ranging professional development component. Imaging Science is an integral element of basic science research and clinical medicine. Imaging cell trafficking and receptor pharmacology in vivo have already led to targeted drug and gene therapies and an understanding of cellular biochemical pathways will contribute to new advances in medicine. Individualized medicine relies heavily on imaging techniques to select the best therapies and monitor progress. Although structural in situ human imaging is already a critical component of clinical medicine, many advances are needed in functional imaging of the brain and other organs to improve healthcare. President Obama has recently allocated $100M to research on brain mapping that relies heavily on imaging. We have identified a critical need for imaging scientists to develop new imaging instrumentation and apply that instrumentation with appropriate informatics and data mining. This training program will have a high impact on basic science and clinical medicine by providing the next generation of imaging scientists in academia, industry and national labs. This training program fills a criticl niche by providing highly skilled scientists who are trained in the broad trajectory of imaging science with a coherent training focus. This program intentionally has the breadth for our graduates to choose career pathways that require any or all aspects of imaging science. Understanding the interplay between the instrumentation and informatics is important for designing the next generation of hardware and software tools for quantifying structure and function in complex biological systems.